Alteration of synaptic activity-regulating genes underlying functional improvement by long-term exposure to an enriched environment in the adult brain

Min Young Lee, Ji Hea Yu, Ji Yeon Kim, Jung Hwa Seo, Eun Sook Park, Chul Hoon Kim, Hyongbum Kim, Sung Rae Cho

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background. Housing animals in an enriched environment (EE) enhances behavioral function. However, the mechanism underlying this EE-mediated functional improvement and the resultant changes in gene expression have yet to be elucidated. Objectives. We attempted to investigate the underlying mechanisms associated with long-term exposure to an EE by evaluating gene expression patterns. Methods. We housed 6-week-old CD-1 (ICR) mice in standard cages or an EE comprising a running wheel, novel objects, and social interaction for 2 months. Motor and cognitive performances were evaluated using the rotarod test and passive avoidance test, and gene expression profile was investigated in the cerebral hemispheres using microarray and gene set enrichment analysis (GSEA). Results. In behavioral assessment, an EE significantly enhanced rotarod performance and short-term working memory. Microarray analysis revealed that genes associated with neuronal activity were significantly altered by an EE. GSEA showed that genes involved in synaptic transmission and postsynaptic signal transduction were globally upregulated, whereas those associated with reuptake by presynaptic neurotransmitter transporters were downregulated. In particular, both microarray and GSEA demonstrated that EE exposure increased opioid signaling, acetylcholine release cycle, and postsynaptic neurotransmitter receptors but decreased Na+/Cl - dependent neurotransmitter transporters, including dopamine transporter Slc6a3 in the brain. Western blotting confirmed that SLC6A3, DARPP32 (PPP1R1B), and P2RY12 were largely altered in a region-specific manner. Conclusion. An EE enhanced motor and cognitive function through the alteration of synaptic activity-regulating genes, improving the efficient use of neurotransmitters and synaptic plasticity by the upregulation of genes associated with postsynaptic receptor activity and downregulation of presynaptic reuptake by neurotransmitter transporters.

Original languageEnglish
Pages (from-to)561-574
Number of pages14
JournalNeurorehabilitation and Neural Repair
Volume27
Issue number6
DOIs
Publication statusPublished - 2013 Jul 1

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Neurotransmitter Transport Proteins
Brain
Genes
Short-Term Memory
Animal Housing
Down-Regulation
Rotarod Performance Test
Gene Expression
Inbred ICR Mouse
Dopamine Plasma Membrane Transport Proteins
Neurotransmitter Receptor
Neuronal Plasticity
Cerebrum
Microarray Analysis
Interpersonal Relations
Transcriptome
Synaptic Transmission
Running
Cognition
Opioid Analgesics

All Science Journal Classification (ASJC) codes

  • Rehabilitation
  • Neurology
  • Clinical Neurology

Cite this

Lee, Min Young ; Yu, Ji Hea ; Kim, Ji Yeon ; Seo, Jung Hwa ; Park, Eun Sook ; Kim, Chul Hoon ; Kim, Hyongbum ; Cho, Sung Rae. / Alteration of synaptic activity-regulating genes underlying functional improvement by long-term exposure to an enriched environment in the adult brain. In: Neurorehabilitation and Neural Repair. 2013 ; Vol. 27, No. 6. pp. 561-574.
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abstract = "Background. Housing animals in an enriched environment (EE) enhances behavioral function. However, the mechanism underlying this EE-mediated functional improvement and the resultant changes in gene expression have yet to be elucidated. Objectives. We attempted to investigate the underlying mechanisms associated with long-term exposure to an EE by evaluating gene expression patterns. Methods. We housed 6-week-old CD-1 (ICR) mice in standard cages or an EE comprising a running wheel, novel objects, and social interaction for 2 months. Motor and cognitive performances were evaluated using the rotarod test and passive avoidance test, and gene expression profile was investigated in the cerebral hemispheres using microarray and gene set enrichment analysis (GSEA). Results. In behavioral assessment, an EE significantly enhanced rotarod performance and short-term working memory. Microarray analysis revealed that genes associated with neuronal activity were significantly altered by an EE. GSEA showed that genes involved in synaptic transmission and postsynaptic signal transduction were globally upregulated, whereas those associated with reuptake by presynaptic neurotransmitter transporters were downregulated. In particular, both microarray and GSEA demonstrated that EE exposure increased opioid signaling, acetylcholine release cycle, and postsynaptic neurotransmitter receptors but decreased Na+/Cl - dependent neurotransmitter transporters, including dopamine transporter Slc6a3 in the brain. Western blotting confirmed that SLC6A3, DARPP32 (PPP1R1B), and P2RY12 were largely altered in a region-specific manner. Conclusion. An EE enhanced motor and cognitive function through the alteration of synaptic activity-regulating genes, improving the efficient use of neurotransmitters and synaptic plasticity by the upregulation of genes associated with postsynaptic receptor activity and downregulation of presynaptic reuptake by neurotransmitter transporters.",
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Alteration of synaptic activity-regulating genes underlying functional improvement by long-term exposure to an enriched environment in the adult brain. / Lee, Min Young; Yu, Ji Hea; Kim, Ji Yeon; Seo, Jung Hwa; Park, Eun Sook; Kim, Chul Hoon; Kim, Hyongbum; Cho, Sung Rae.

In: Neurorehabilitation and Neural Repair, Vol. 27, No. 6, 01.07.2013, p. 561-574.

Research output: Contribution to journalArticle

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AU - Lee, Min Young

AU - Yu, Ji Hea

AU - Kim, Ji Yeon

AU - Seo, Jung Hwa

AU - Park, Eun Sook

AU - Kim, Chul Hoon

AU - Kim, Hyongbum

AU - Cho, Sung Rae

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N2 - Background. Housing animals in an enriched environment (EE) enhances behavioral function. However, the mechanism underlying this EE-mediated functional improvement and the resultant changes in gene expression have yet to be elucidated. Objectives. We attempted to investigate the underlying mechanisms associated with long-term exposure to an EE by evaluating gene expression patterns. Methods. We housed 6-week-old CD-1 (ICR) mice in standard cages or an EE comprising a running wheel, novel objects, and social interaction for 2 months. Motor and cognitive performances were evaluated using the rotarod test and passive avoidance test, and gene expression profile was investigated in the cerebral hemispheres using microarray and gene set enrichment analysis (GSEA). Results. In behavioral assessment, an EE significantly enhanced rotarod performance and short-term working memory. Microarray analysis revealed that genes associated with neuronal activity were significantly altered by an EE. GSEA showed that genes involved in synaptic transmission and postsynaptic signal transduction were globally upregulated, whereas those associated with reuptake by presynaptic neurotransmitter transporters were downregulated. In particular, both microarray and GSEA demonstrated that EE exposure increased opioid signaling, acetylcholine release cycle, and postsynaptic neurotransmitter receptors but decreased Na+/Cl - dependent neurotransmitter transporters, including dopamine transporter Slc6a3 in the brain. Western blotting confirmed that SLC6A3, DARPP32 (PPP1R1B), and P2RY12 were largely altered in a region-specific manner. Conclusion. An EE enhanced motor and cognitive function through the alteration of synaptic activity-regulating genes, improving the efficient use of neurotransmitters and synaptic plasticity by the upregulation of genes associated with postsynaptic receptor activity and downregulation of presynaptic reuptake by neurotransmitter transporters.

AB - Background. Housing animals in an enriched environment (EE) enhances behavioral function. However, the mechanism underlying this EE-mediated functional improvement and the resultant changes in gene expression have yet to be elucidated. Objectives. We attempted to investigate the underlying mechanisms associated with long-term exposure to an EE by evaluating gene expression patterns. Methods. We housed 6-week-old CD-1 (ICR) mice in standard cages or an EE comprising a running wheel, novel objects, and social interaction for 2 months. Motor and cognitive performances were evaluated using the rotarod test and passive avoidance test, and gene expression profile was investigated in the cerebral hemispheres using microarray and gene set enrichment analysis (GSEA). Results. In behavioral assessment, an EE significantly enhanced rotarod performance and short-term working memory. Microarray analysis revealed that genes associated with neuronal activity were significantly altered by an EE. GSEA showed that genes involved in synaptic transmission and postsynaptic signal transduction were globally upregulated, whereas those associated with reuptake by presynaptic neurotransmitter transporters were downregulated. In particular, both microarray and GSEA demonstrated that EE exposure increased opioid signaling, acetylcholine release cycle, and postsynaptic neurotransmitter receptors but decreased Na+/Cl - dependent neurotransmitter transporters, including dopamine transporter Slc6a3 in the brain. Western blotting confirmed that SLC6A3, DARPP32 (PPP1R1B), and P2RY12 were largely altered in a region-specific manner. Conclusion. An EE enhanced motor and cognitive function through the alteration of synaptic activity-regulating genes, improving the efficient use of neurotransmitters and synaptic plasticity by the upregulation of genes associated with postsynaptic receptor activity and downregulation of presynaptic reuptake by neurotransmitter transporters.

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